Enhanced and persistent levels of interleukin (IL)-17+CD4+ T cells and serum IL-17 in patients with early inflammatory arthritis

Gullick, Nicola; Abozaid, Hanan S.; Jayaraj, David M.; Evans, Hayley G.; Scott, David; Choy, Ernest; Taams, Leonie S.

doi:10.1111/cei.12167

Cited by 48 publications

(36 citation statements)

References 41 publications

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“…In a random subset of patients in our cohort who did not receive induction treatment, longitudinal IL-17A levels did not fluctuate significantly over several years of observation. While an increase in cytokine levels over time in the general population has been described and considered to represent unhealthy aging due to underlying inflammatory processes (41), in a cohort of early arthritis patients, there was no significant change in IL-17A over a series of developmental stages (40).…”

Section: Discussionmentioning

confidence: 90%

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IL-17A levels in systemic lupus erythematosus associated with inflammatory markers and lower rates of malignancy and heart damage: Evidence for a dual role

Raymond¹,

Ostli-Eilertsen²,

Griffiths³

et al. 2017

Eur J Rheumatol

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Objective: The interleukin 17 (IL-17) cytokine family is involved in a number of chronic inflammatory diseases. In spite of contradictory findings and a lack of causality in clinical studies, IL-17 inhibition for systemic lupus erythematosus (SLE) has regained attention as a potential therapeutic pathway, after demonstrating disease-modifying capabilities in ankylosing spondylitis. We investigated the clinical associations of interleukin 17 A (IL-17A) in patients with SLE.Material and Methods: A cross-sectional study was performed involving SLE patients (n=102; age: 49 years; 86% female) recruited from a regional registry. IL-17A levels were determined by immunoassay, disease activity by Systemic Lupus Erythematosus Disease Activity Index-2K (SLEDAI-2K), and cumulative damage by Systemic Lupus International Collaborative Clinics Damage Index (SDI) scores. Non-parametric techniques were used to examine the association between IL-17A and disease activity and autoantibody profiles were compared with healthy controls (n=31): principal component analysis (PCA) was used to determine the interplay of immune cells across disease states and damage development in SLE patients.Results: SLE patients had higher IgG levels, lower T-cell and B-cell counts, but median IL-17A levels did not differ from the controls (28.4 vs. 28.4 pg/mL, p=0.9). In SLE patients, IL-17A did not correlate with SLEDAI-2K or SDI, but was inversely related with age (correlation coefficients, Rs.=-0.29, p<0.05), systolic blood pressure (Rs.=-0.31, p<0.05), years of smoking (Rs.=-0.43, p<0.05), cumulative heart (Rs.=-0.22, p<0.05), and malignancy damage (Rs.=-0.18, p<0.05). Serological correlations for IL-17A existed with immunoglobulin G (IgG) levels (Rs.=0.21, p<0.05), high sensitivity C-reactive protein (hs-CRP) levels (Rs.=0.28, p<0.05), proteinuria (Rs.=0.64, p<0.05), and pre-albumin (Rs.=-0.22, p<0.05). Longitudinal data showed only modest fluctuation in IL-17A levels, independent of SLEDAI-2K. Conclusion:These results suggest that IL-17A, while participating in inflammation, may also serve a protective purpose in SLE patients.

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Section: Discussionmentioning

confidence: 90%

“…There is a dearth of evidence regarding the long-term course of cytokines, including IL-17A, in SLE patients (40). Zickert et al (5) showed that IL-17A levels were reduced 7 months after cyclophosphamide-based induction treatment for LN.…”

Section: Discussionmentioning

confidence: 99%

IL-17A levels in systemic lupus erythematosus associated with inflammatory markers and lower rates of malignancy and heart damage: Evidence for a dual role

Raymond¹,

Ostli-Eilertsen²,

Griffiths³

et al. 2017

Eur J Rheumatol

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“…Additional studies aimed to address the percentage of circulating Th17 cells in pSS are currently lacking. In other chronic autoimmune diseases, such as RA, currently available data concerning conventional CD4 + Th17 cells in early phases of the disease are conflicting, reporting either increase or decrease of this T-cell subset [63,64] and it is conceivable that different disease duration in patient cohort may account for such discrepancies.…”

Section: Il-17 Axis and Th17 Cells In Pssmentioning

confidence: 99%

Unmasking the pathogenic role of IL-17 axis in primary Sjögren's syndrome: A new era for therapeutic targeting?

Alunno

Carubbi

Bartoloni

et al. 2014

Autoimmunity Reviews

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“…Major progress has been made in the understanding of the molecular mechanisms responsible for autoimmunity, including the identification of T helper type 17 (Th17) effector response as a key player in the pathogenesis of multiple sclerosis (MS) [2,3] and rheumatoid arthritis (RA) [4,5] and the recognition of type I interferons as critical mediators in the development of systemic lupus erythematosus (SLE) [6,7]. However, unlike the outstanding advances introduced in the treatment and prognosis of RA and MS with the development of biological agents, the field has not had a substantial breakthrough in the design of new therapies for SLE [8,9].…”

Section: Introductionmentioning

confidence: 99%

Carbon monoxide inhibits T cell activation in target organs during systemic lupus erythematosus

Mackern-Oberti

Obreque

Méndez

et al. 2015

Clinical and Experimental Immunology

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SummarySystemic lupus erythematosus is characterized by the presence of circulating anti-nuclear antibodies (ANA) and systemic damage that includes nephritis, haematological manifestations and pulmonary compromise, among others. Although major progress has been made in elucidating the molecular mechanisms responsible for autoimmunity, current therapies for lupus have not improved considerably. Because the exposure of carbon monoxide (CO) has been shown to display beneficial immunoregulatory properties in different immune-mediated diseases, we investigated whether CO therapy improves lupus-related kidney injury in lupus mice. MRL-Fas lpr lupus mice were exposed to CO and disease progression was evaluated. ANA, leucocyteinfiltrating populations in spleen, kidney and lung and kidney lesions, were measured. CO therapy significantly decreased the frequency of activated B220 1 CD4 2 CD8 2 T cells in kidneys and lungs, as well as serum levels of ANA. Furthermore, we observed that CO therapy reduced kidney injury by decreasing proliferative glomerular damage and immune complexes deposition, decreased proinflammatory cytokine production and finally delayed the impairment of kidney function. CO exposure ameliorates kidney and lung leucocyte infiltration and delays kidney disease in MRLFas lpr lupus mice. Our data support the notion that CO could be explored as a potential new therapy for lupus nephritis.

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Enhanced and persistent levels of interleukin (IL)-17+CD4+ T cells and serum IL-17 in patients with early inflammatory arthritis

Abstract: SummaryPrognosis of patients with early inflammatory arthritis (EIA) is highly variable. The aim of this study was to compare, longitudinally and crosssectionally, the levels of cytokine-expressing cells in peripheral blood (

Cited by 48 publications

References 41 publications

IL-17A levels in systemic lupus erythematosus associated with inflammatory markers and lower rates of malignancy and heart damage: Evidence for a dual role

IL-17A levels in systemic lupus erythematosus associated with inflammatory markers and lower rates of malignancy and heart damage: Evidence for a dual role

Unmasking the pathogenic role of IL-17 axis in primary Sjögren's syndrome: A new era for therapeutic targeting?

Carbon monoxide inhibits T cell activation in target organs during systemic lupus erythematosus

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